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Acute effect of L‐796568, a novel β 3 ‐adrenergic receptor agonist, on energy expenditure in obese men
Author(s) -
Baak Marleen A.,
Hul Gabby B. J.,
Toubro Søren,
Astrup Arne,
Gottesdiener Keith M.,
DeSmet Marina,
Saris Wim H. M.
Publication year - 2002
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1067/mcp.2002.122527
Subject(s) - endocrinology , medicine , agonist , respiratory quotient , heart rate , placebo , crossover study , blood pressure , propranolol , lipolysis , chemistry , receptor , adipose tissue , alternative medicine , pathology
Objective Our objective was to investigate the thermogenic efficacy of single oral doses of the novel β 3 ‐adrenergic receptor agonist L‐796568 [( R )‐ N ‐[4‐[2‐[[2‐hydroxy‐2‐(3‐pyridinyl)ethyl]amino]ethyl]‐phenyl]‐4‐[4‐[4‐(trifluoromethyl)phenyl]thiazol‐2‐yl]‐benzenesulfonamide, dihydrochloride] inhumans. Methods Twelve healthy overweight to obese men participated in this 2‐center, 3‐period, randomized, placebo‐controlled, crossover trial. In each period subjects received 250 mg L‐796568, 1000 mg L‐796568, or placebo. Energy expenditure and respiratory quotient were determined by indirect calorimetry; blood samples were taken; and ear temperature, heart rate, and blood pressure were measured at baseline and during the 4‐hour period after administration. Results Energy expenditure increased significantly after the 1000‐mg dose (about 8%) and this was accompanied by an increase in plasma glycerol and free fatty acid concentrations. Systolic blood pressure also increased significantly. No changes in heart rate, diastolic blood pressure, ear temperature, plasma catecholamine, potassium, orleptin were found. Conclusions Single‐dose administration of 1000 mg of the novel β 3 ‐adrenergic receptor agonist L‐796568 increased lipolysis and energy expenditure in overweight men. This is the first study to show such an effect of β 3 ‐adrenergic receptor agonists in humans without significant evidence for β 2 ‐adrenergic receptor involvement. Clinical Pharmacology & Therapeutics (2002) 71 , 272–279; doi: 10.1067/mcp.2002.122527